Immunoprecipitation and pull-down assays are workhorses in biochemistry. With the ability to discriminate specific substrates in heterogeneous mixtures, they play important roles in a wide range of fields, including proteomics, epigenomics and transcriptomics. However, despite their broad utility, these well-established strategies have limitations. Besides requiring large sample sizes, they are labor-intensive and are not inherently quantitative, typically requiring subsequent PCR or enrichment for downstream analysis. For these reasons, quantitative technologies with single-molecule sensitivity may offer important advantages.